ANALYSIS OF 4-HYDROXYCYCLOPHOSPHAMIDE IN CANCER PATIENTS PLASMA FOR THERAPEUTIC DRUG MONITORING OF CYCLOPHOSPHAMIDE

  • Yahdiana Harahap Laboratory of Bioavailability and Bioequivalence, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia 16424
  • Christian Samuel Laboratory of Bioavailability and Bioequivalence, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia 16424
  • Rizka Andalusia Department of Research and Development, “Dharmais” Cancer Hospital, Jakarta, Indonesia
  • Nadia Farhanah Syafhan Laboratory of Bioavailability and Bioequivalence, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia 16424

Abstract

Objective: To quantify 4-hydroxycyclophosphamide in cancer patients’ plasma for therapeutic drug monitoring of cyclophosphamide.

Methods: The blood was collected at 0.5 and 1 h after administration of chemotherapy. Prior to analysis, 4-OHCP in plasma was derivatized with semicarbazide HCl, then was extracted using 4 ml ethyl acetate and finally was determined by Ultra High-Performance Liquid Chromatography–tandem mass spectrometry. Chromatographic separation was conducted using waters acquity BEH C18 column (1.7 μm; 50 mm x 2.1 mm). The mobile phase consisted of formic acid 0.1% and methanol (50: 50, v/v), column temperature 30 °C and flow rate of 0.3 ml/min. Mass detection was performed on waters xevo TQD equipped with an electrospray ionization (ESI) source at positive ion mode in the multiple reaction monitoring (MRM). Cyclophosphamide was detected at m/z 260.968>139.978, 4-hydroxycyclophosphamide-semicarbazide at m/z 338.011>224.97, and hexamethylphosphoramide as internal standard at m/z 180.17>92.08.

Results: The method was linear in the range of 5–1000 ng/ml for cyclophosphamide and also for 4-hydroxycyclophosphamide. The results showed that the level of 4-OHCP in 39 cancer patients was in the range of 5.02 ng/ml to 832.44 ng/ml.

Conclusion: 4-hydroxycyclophosphamide was detected on 39 patient samples with the lowest level of 5.40ng/ml and the highest level was 832.44 ng/ml. This can be a parameter that the regiment of cyclophosphamide was effective.

Keywords: Cancer, Cyclophosphamide, 4-hydroxycyclophosphamide, Hexamethylphosphoramide, LC-MS/MS

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How to Cite
Harahap, Y., C. Samuel, R. Andalusia, and N. F. Syafhan. “ANALYSIS OF 4-HYDROXYCYCLOPHOSPHAMIDE IN CANCER PATIENTS PLASMA FOR THERAPEUTIC DRUG MONITORING OF CYCLOPHOSPHAMIDE”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 9, Sept. 2016, pp. 194-00, doi:10.22159/ijpps.2016v8i9.12918.
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